How Extending Patent Protection For Antibiotics Creates Perverse Incentives To Render Them Useless

from the monopolizing-ourselves-to-death dept

We take antibiotics and their ability to kill practically all bacteria for granted. But scientists are increasingly warning that we may be about to leave what might come to be seen as a golden age for anti-bacterial drugs, and enter a post-antibiotic era. As the World Health Organization’s Director-General said, quoted in an article on the Citizen Vox site:

"A post-antibiotic era means, in effect, an end to modern medicine as we know it. Things as common as strep throat or a child’s scratched knee could once again kill."

The problem arises from natural selection. The more we use an antibiotic -- especially if we use it carelessly, failing to complete the full course -- the more we select for bacteria that are partially resistant to it. Over time, those bacteria thrive, displacing bacteria that are unable to withstand the antibiotic. Eventually, bacteria that are completely resistant to that particular drug are likely to evolve -- a situation that can have dire consequences. For example, even five years ago, methicillin-resistant Staphylococcus Aureus (MRSA) was killing more people in the US annually than AIDS.

The obvious way to mitigate this problem is to reduce the use of antibiotics, saving them for truly life-threatening situations, and that's what's happening to a certain extent in Europe:

To preserve the effectiveness of antibiotics for human use, Europe banned feeding antibiotics to livestock for growth promotion in 2006. In Denmark, where such use of antibiotics had been phased out more than a decade ago, drug-resistant pathogens in livestock are down while industry output is up.

As the Citizen Vox article notes, a similar proposal to restrict the use of antibiotics has not gone very far in the US, partly because an alternative approach has found far more favor, for evident reasons:

the Generating Antibiotic Incentives Now, or GAIN, Act has piggybacked into the FDA bill reauthorizing user fees for drug approval. GAIN would provide five more years of monopoly protections for new antibiotics. Already receiving three to seven years of exclusivity, some antibiotics may receive up to 10 years of protection after market approval. This measure defies both the economics and biology of antibiotic resistance.

The reason for that comes down to the nature of patents. Since they are time-limited, their owners have a natural incentive to exploit them as fully as possible during their entire term, when they can charge elevated monopoly prices. For other kinds of patents, that might be regrettable from an economic viewpoint, but it's hardly a matter of life or death. For antibiotics it's more problematic.

The more holders of patents for antibiotics seek to maximize their profits by boosting production and selling them as widely as possible, the more antibiotic resistance is likely to develop -- especially if they are given to livestock as well as humans. That growing resistance is a classic negative externality -- it's not something the pharma company needs to worry about, since the cost will come later and be borne by the general population in the form of increased medical expenses, longer stays in hospital, more serious infections and higher mortality rates.

Antibiotics are perhaps the clearest example of how the interests of patent holders are not only misaligned with those of the public, but are diametrically opposed to them in some cases. Although, in the short term, patents may encourage more antibiotics to be developed, in the long term they undermine their effectiveness. Even more than for drugs in general, antibiotics are an area where we need different kinds of incentives to stimulate development of new drugs -- government-funded prizes, perhaps.

here's a good start

Let's prohibit livestock producers from dumping vast amounts of antibiotics into feed. Considering what this alone is doing to the effectiveness of antibiotics, these businesses could almost be accused of crimes against humanity.

Right -- I know it's not going to happen, any more than we're going to ween ourselves off non-renewable energy sources like oil or coal. Some men just want to watch the world burn out.

Re: here's a good start

As the late, great George Carlin said, the world's not going away, it's doing fine. WE'RE fucked. Pack your shit, folks. We've served our purpose and are going to be shaken off like a surface nuisance.

Re: Re: Re: here's a good start

That logic works until you realize that God is Mother Nature and that all the offenses against mother nature are all acts against God and (s)he isn't coming for you when we are wiped from the face of the earth.

Re: Re: Re: here's a good start

Don't be ridiculous. What evidence do you have that the companies doing this are run by people who even claim to be Christian, let alone do anything to live up to that claim? Seems to me that the only people capable of doing something like this are those who truly believe they'll have nobody to answer to.

Re: Re: Re: Re: Re: here's a good start

Actually, I *have* read my Old Testament. In more than one language, even. And it says that man was given everything on earth as his stewardship.

And in fact, I've also read my New Testament, in more than one language, and it says that an accounting of every man's stewardship will be required at his hand, and that the Lord will be very displeased with those who served as poor or unwise stewards.

So what was your point again, and how is one senator taking a certain passage completely out of context and using his (laughable) personal interpretation (which is also forbidden by the New Testament) for political gain relevant in any way?

Re: Re: Re: Re: Re: Re: here's a good start

Wow. Just wow.
I was explaining the mentality of these individuals, and how they justify their behavior to themselves and others like them.

Some quotes:

In the beginning "...God said, “Let Us make man in Our image, according to Our likeness; let them have dominion over the fish of the sea, over the birds of the air, and over the cattle, over all the earth and over every creeping thing that creeps on the earth (Gen. 1:26)."

...Then God blessed them, and God said to them, “Be fruitful and multiply; fill the earth and subdue it; have dominion over the fish of the sea, over the birds of the air, and over every living thing that moves on the earth (Gen. 1:28).”

And after the Great Flood where the whole world was destroyed, but for eight people (Noah and his wife, and their sons and their wives) and a boat-full of animals, GOD again gave man rule over HIS creation. In Genesis 9:2 it reads, "And the fear of you and the dread of you shall be on every beast of the earth, on every bird of the air, on all that move on the earth, and on all the fish of the sea. They are given into your hand."

These passages and others like them are used to justify exhausting the resources of the earth. Do I consider it right? No. But it is a fact that this is how some people interpret them.

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But they're misunderstanding the obvious meaning of those passages: they don't say that man owns everything and can do whatever he wants with them. They say that man is the caretaker of God's property.

Re: Re: Re: Re: Re: Re: Re: Re: Re: Re: Re: here's a good start

Well it's a legal requirement in Australia to show where any and al food products come from (ie: country of origin) unless they are manufactured in Aust from foreign ingredients and local ingredients (which is pretty ambiguous) though it still needs to state the 'foreign' part, just not origin. Since full meat (not processed meats) is not made of different parts then the origin of the meat has to be shown.

How do we get away with this? easy. Our Quarantine laws are one the strictest in the world (New Zealand being strictest) and meat and its by-products is a high-risk quarantine item. This is why we still do not have Mad cow disease, foot in mouth or other major cattle, livestock diseases in Australia.

The WTO treaty is still in place though the quarantine laws pre-date the treaty by nearly 50 yrs (or more) and are part of our constitution as well. Therefore that part of WTO orders (if they made them) are moot, Europe has same ability.

I still don't get how patents are contributing to anti-biotic resistant diseases. Patents would cause these products to be used less which will slow down the resistance process. Unless you are arguing that increased prices somehow encourages people to misuse the anti-biotics, ie: by taking fewer anti-biotics because of the price (or maybe sharing doses with others instead of taking the full dose/treatment). Possible ... but unlikely?

Re:

The argument is that, since patents have a limited life-span, pharma companies are encouraged to push the products and much as possible, as quickly as possible, to make the most money as possible before the patent lapses and they're forced to compete. That would encourage those companies to encourage reckless and near-indiscriminate use of those antibiotics in situations where other methods might have been more appropriate.

TL;DR It discourages prolonging the effectiveness of antibiotics by encouraging immediate use and short term sales.

Ok. I live in Denmark and I know the secret ingredient used instead of antibiotics in pork-production...
It is incredibly simple to avoid using the antibiotic and only treat the ill animals and the increase in lenght of feeding-period is small and it is not necessarily expensive.

Re:

Another method is the usage of Phage therapy which is the use of bacteriophages to treat bacterial infections, which makes sense since bacteriophages are the natural predators (for want of a better word) of specific bacterium.

Eastern Europe (specifically Georgia) has been using this for decades and its quite interesting research.

Really Tech Dirt?

The solution is obviously to abolish patents so the market can be flooded with dozens of generic versions of the same antibiotic. When an unlimited number of suppliers can produce the antibiotic, there will clearly be a drastic decrease in the use of antibiotic compared to when there is only one supplier. Obviously, a super cheap generic antibiotic won't be overprescribed the same way expensive patented antibiotics are.

Re: Really Tech Dirt?

Perhaps. But when there's no longer a strong lobby effort by Big Pharma to discourage regulations on the use of antibiotics, or as strong a marketing effort by Big Pharma on either doctors or potential patients. Then, regardless of the price and availability of the antibiotics, reasonable efforts to curtail overuse of antibiotics can be put into place.

Medicine will be cheaper and used more responsibly: a win-win scenario. Unless you're Big Pharma, of course.

Re: Really Tech Dirt?

This is one area where we completely agree.

However, there does need to be some sense of rationality when it comes to who gets what patent for how long. Software patents are ridiculous. Software is equivalent to a thought process. If it deserves any patent protection, it should be very very limited.

We don't, and probably never will, have a silicon shortage. Silicon is the third most common element on the earth. It is wonderful that we can make many great advances with silicon that will help us all have better lives, but does rationing through the patent process make sense? The limiting factor to most silicon and/or carbon technologies that may replace it are probably going to be energy costs. Therefore, if limited rationing needs to be done it should always encourage the more energy efficient technology and not limit its widespread adoption. This is especially true since less efficient technologies are already out of patent and could be reproduced anywhere.

Humanity is starting to realize that critical shortages may soon affect our food and medical supplies worldwide. Sane intellectual property laws could help us navigate these problems. The current system is broken.

A bit more complicated

Upfront disclosure: I work as a researcher in the pharmaceutical industry, and have worked on anti-microbial projects in the past. Whether this provides me with insight or bias is left as an exercise to the reader.

This increased patent life incentive is actually separated quite a bit from the issue of antibiotics being overused. The vast majority of commonly-used antibiotics are off patent, and have been for a while. As a result of this many of them are dirt cheap (and for the ones that aren't this is only due to manufacturing costs). This fact isn't going to be changed by any increase in patent length (short of putting these drugs back on patent, which would be a really stupid thing to do), and the wide use of these drugs isn't going to be affected by increasing patent length for new antibiotics.

However, decreasing the use of existing antibiotics isn't the purpose of this patent extension. Rather, the purpose is to provide increased financial incentives for the creation of new antibiotics (targeting those strains that current antibiotics tend to fall down against). Currently in the pharma industry trying to develop a new antibiotic is generally considered a poor investment due to fact that new antibiotics tend to not make much money. This is because all those existing antibiotics (that are off patent) are pretty damn good- they're cheap, they're safe, and against the vast majority of infections they're quite effective. New antibiotics tend to be relegated to use against the small number of cases that the old antibiotics fail against; this is a small and not particularly profitable market (and unlike oncology drugs you typically can't get away with charging absolutely obscene prices for antibiotics). The thought with this patent extension is that a few more years of exclusivity will provide enough of a financial incentive for pharma companies to start reinvesting in the development of new antibiotics.

That said, I think that this extension is a bad idea and won't actually accomplish anything meaningful. For new antibiotics with very small markets the increased period of exclusivity still won't be enough to make them good investments, and if any company comes up with a good enough idea for a new antibiotic that would be a financial success (broad spectrum, new mechanism of action, excellent resistance profile, spotless safety profile- a combination extremely difficult to achieve) the drug would be quite profitable even without the extension and all the extension will have accomplished is keeping the prices of the drug higher for a longer period.

A much better approach, in my opinion, would be for the government to offer subsidies for antibiotics that meet a target product profile and which make it through the approval process. Pharma companies would still need to take the risk of investing in research of the drugs (and wouldn't get anything unless they succeeded), but they would know that if they succeeded they'd be able to recoup their investment, and the drug would still fall off patent in the same amount of time as all other drugs. Of course, with such an approach there's the risk of regulatory capture (e.g. the FDA putting out TPPs tailored to projects that specific pharma companies already have going), or regulators not aligning the TPPs with what drugs are actually needed (and this one can be quite difficult, as no one really knows what bacterial resistance profiles will look like in ten years time, which is about the earliest you can expect a drug project started today to come to market).

And of course, this all assumes that the government should be providing financial incentives for specific classes of drugs to begin with. I'm personally of the opinion that promoting the development of drugs that save lives but target a small enough population that free-market solutions won't result in their development is just the kind of thing that government should be doing, but I realize there can be extensive debate on this point. So overall it's a pretty complicated situation with no slam-dunk solutions, and the original write-up barely even scratches the surface of it.

Re: A bit more complicated

Brilliant and highly informative analysis. Thankyou

Another approach that governments (and the medical profession) needs to apply that should be mentioned is Education.

People need to be made to understand when they should and shouldn't be using these antibiotics and common sense approaches to pro-actively stop these bacterium infections and spread of viral strains (though that's a separate issue by itself).

The amount of people overloading on drugs for no obvious reason other than they think or they were told by advertisements about the latest cough medicine or paracetamol on the market and how it will "cure" them (of course see your doctor if pain persists) of all life's ills.

General Practitioners are sometimes as bad here too, proscribing antibiotics for self evident viral infections just to create the placebo affect in their patients (or stroke their fears) is plain wrong and needs to be legislated out..

Also IMHO some of the problem lies in how we (in the western world) are now going clean mad. Wehn you see on advertisements how the latest cleaning product for your home, office, garage, etc now kills 99.9% of bacteria I sometimes wonder if that .1% is the stuff that the other 99.9% was keeping at bay since that .1% will kill ya dead!
(Note: I am not talking about cleaning of hospitals and other clean-room environments and the problems they have with superbugs at moment.. though its a problem too)

Re: Re: A bit more complicated

Education is a rather difficult route to go, as most people just aren't interested enough to change their behaviors regarding things they can't see direct results from. Even simple things like patient compliance (e.g. completing dosing regiments) pose a constant challenge for physicians, and that's with a pharmacist individually explaining to every person that it's important for them to keep taking the pills until they're all gone.

There are also significant financial incentives for some of the worst offenders when it comes to the overuse of antibiotics. For instance, large livestock operations use a tremendous amount of antibiotics to keep disease under control in their herds, and a significant portion of these antibiotics end up getting washed into the environment where they contribute to the evolution of resistant strains. The livestock operations use such large amounts of antibiotics because it allows them to keep their herds in much more cramped conditions (cheaper) without disease running rampant as a result. This is the kind of thing that can only be fixed by regulations limiting the practice.

Overuse of antibiotics by people, such as you mentioned, is definitely another area that needs to be addressed. Direct to customer (DTC) advertising has contributed to this in part (and for the record I think DTC advertising is an abomination that needs to be gotten rid of, but that's another discussion), and is compounded by patients who will demand antibiotics from their doctors for things like the cold (which antibiotics won't help with), and unfortunately some doctors will give them what they want just to avoid the hassle of having to argue with them. A final thing to keep in mind is that once resistant bacterial infections start to appear, the most common place for these infections to get transmitted is in hospitals, due to proximity, people having weakened immune systems, resistant infection patients not being properly identified and isolated, and proper hygiene procedures not being followed.

For solving these various problems, Norway is a good country to look to as an example, and their efforts have resulted in them having one of the lowest rates of MRSA infections in the world. Their approach involved several government initiatives. The amount of antibiotics that could be used on livestock was restricted, and new rules were set regarding how much doctors could prescribe antibiotics (e.g. they couldn't be prescribed for confirmed viral infections such as the cold). More stringent rules were also set for hospital hygiene, and greater efforts were made to quickly identify and isolate MRSA patients.

Finally, since you mentioned anti-bacterial cleaners, I'll say that those are also contributing to the problem. Now, it's important to note that there's a big difference between regular cleaners/soaps/detergents, which are already highly lethal to bacteria (and you're not going to see bacteria developing resistance to detergents or bleach), and "anti-bacterial" cleaners which include some level of antibiotics in a completely pointless and counterproductive move to appeal to customers' phobias surrounding bacteria. As for the 99.9% killed vs the 0.1% survived, the characteristics of the survivors depend on what did the killing. For something indiscriminate like bleach you'll just be looking at a statistical sample of whatever was in the original culture, while if there was an antibiotic present you'll definitely see an increase in the proportion of bacteria with resistance to that antibiotic. It should be noted, though, that antibiotic resistance isn't necessarily associated with greater virulence, or even greater overall fitness. In fact many resistant strains actually have less overall fitness as they're expending resources on their resistance mechanisms while non-resistant strains aren't. It's just that if one of those resistant strains manages to take hold in someone's body it's much more difficult for us to treat.

Re: A bit more complicated

Disclosure: I have a Masters degree in molecular biology, worked for a couple of years in biomedical research (biotech and academic) and I am also presently an attorney with a specialization in IP and specifically patent law.

I think the post by DarkPhoenix was a very thoughtful and an insightful one. In fact, much more so than the idiotic article itself and vastly more thoughtful than most other comments here, some of which smack of pure conspiracy theories.

I actually agree with just about everything DarkPhoenix said. My comment is really just about one thing: whether extending patent protection would accomplish much.

I agree that in a different society from the one we live in, gov't subsidies for drug development would be the much better way to go. The incentives would be better allocated than under the current profit-driven system, where capturing the bigger share of the market actually allocates incentives in R & D poorly from a utilitarian perspective. Instead of allocating resources (financial and human) towards the development of drugs for rare but dangerous diseases, the resources are being allocated towards development of drugs that are essentially popular on the market. We have multiple PPI drugs; multiple drugs for hypertension; tons of water pills and etc etc. We have very few drugs that target specific cancers, however, because it would be less profitable to go after limited markets.

Having said that, we have the system that we have and we have to formulate policy based on this assumption. And in this context, extending patent protection essentially gives certain pharma companies more financial resources to develop new class of antibiotics. It's an imperfect policy, but we don't live in utopia either. Essentially, the gov't is indirectly giving more money to certain companies and says: if you develop new class of antibiotics, you get to market it as you see fit. And of course it's an established fact that pharma companies will do everything it takes to expand the market as much as possible, including going beyond what the market is "supposed to be" for a particular drug.

Indeed, I am working on a legal case right now against a pharma company, so I see first hand how marketing is done in this industry.

That growing resistance is a classic negative externality -- it's not something the pharma company needs to worry about, since the cost will come later and be borne by the general population in the form of increased medical expenses, longer stays in hospital, more serious infections and higher mortality rates.